Addicted to growth factors?

Abstract

Growth factors appear to limit apoptosis by controlling the abundance or activity of proteins that control the apoptotic process. But that may be only part of the story. Vander Heiden et al. propose an alternative role for growth factors that also appears to influence the tendency of a cell to undergo apoptosis--control of nutrient uptake and bioenergetic homeostasis. In the murine hematopoietic cell line FL5.12, interleukin 3 (IL-3) is required for cell survival. However, the authors found that when the growth factor was withdrawn, it was the magnitude of the decrease in glycolysis, not the amount of growth factor remaining, that seemed to determine whether cells underwent apoptosis. Thus cells used to functioning in the presence of high concentrations of IL-3, which have higher glycolytic rates, were more susceptible to cell death cause by growth factor withdrawal. When availability of glucose to the cells was limited, cytochrome c was released from the mitochondria, cells underwent apoptosis, and sensitivity to such decreases in nutrient availability was again greater in cells "addicted" to a higher concentration of the growth factor. Furthermore, overexpression of the glucose transporter Glut1 (thus supplying the cell with more nutrients) delayed apoptosis caused by growth factor withdrawal. Growth factors can also regulate amounts and activity of glycolytic enzymes, as well as nutrient availability. The authors propose that effects of growth factors on the metabolic status of the cell are likely key factors in determining whether a cell undergoes mitochondrial misfunction leading to apoptosis. M. G. Vander Heiden, D. R. Plas, J. C. Rathmell, C. J. Fox, M. H. Harris, C. B. Thompson, Growth factors can influence cell growth and survival through effects on glucose metabolism. Mol. Cell. Biol. 21 , 5899-5912 (2001). [Abstract] [Full Text]